This project is designed to provide information on basic neural mechanisms involved in the generation and control of respiratory movements in mammals. The long-range goal is to explain the ontogeny and neurogenesis of respiratory movements in terms of the biophysical, synaptic, and network properties of respiratory neurons in the mammalian brainstem and spinal cord. Current work focuses on cellular and network mechanisms generating the respiratory rhythm in the brainstem. A set of interrelated, multi-disciplinary studies are ongoing to determine: sites, cellular components, and architecture of brainstem networks involved in generation and transmission of respiratory rhythm; biophysical properties and synaptic interactions of rhythm-generating neurons; and neurochemical mechanisms for modulation and synaptic transmission of rhythm. Experiments are performed with isolated in vitro brainstem-spinal cord and brainstem slice preparations from fetal, neonatal, and juvenile rodents. The critical brainstem locus containing the populations of neurons generating the rhythm has been identified. Novel in vitro slice preparations containing this critical region and functionally active respiratory networks have been developed which provide a powerful experimental approach for analysis of mechanisms concurrently at cellular and network levels. Computational approaches are being used in parallel to experimental studies to model respiratory neurons and networks. Computational models of the respiratory oscillator have been developed which are allowing analysis of cellular and network mechanisms that are currently difficult to study experimentally.